RHEUMATOID ARTHRITIS

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hi....this ppt is regarding rheumatoid arthritis which is an auto immune disease...i hope this will b useful 4 those pursuing their studies in medical or pharmacy field...

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RHEUMATOID ARTHRITIS:

RHEUMATOID ARTHRITIS BY SHILPA.KANETI ROLL NO.01 M.PHARM (I-SEMESTER) PHARMACY PRACTICE

CONTENTS:

CONTENTS INTRODUCTION EPIDEMOLOGY AETIOLOGY PATHOGENESIS RISK FACTORS DISTINCTIVE CLINICAL FEATURES COMPLICATIONS INVESTIGATIONS TREATMENT Non –Pharmacological pharmacological PREVENTION CONCLUSION REFERENCES

INTRODUCTION :

INTRODUCTION Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints & can also cause inflammation of the tissue around the joints, as well as in other organs in the body. An autoimmune disease is a disease where the immune system attacks healthy parts of the body. As it can affect multiple other organs of the body, RA is referred to as a systemic illness and is sometimes called rheumatoid disease

DIAGRAM SHOWING THE AFFECTED JOINT:

DIAGRAM SHOWING THE AFFECTED JOINT

COMPARISION OF NORMAL JOINT & AFFECTED JOINT:

COMPARISION OF NORMAL JOINT & AFFECTED JOINT

CONTD….:

CONTD …. A joint (the place where two bones meet) is surrounded by a capsule that protects and supports & it is lined with a type of tissue called Synovium , which produces synovial fluid that lubricates and nourishes joint tissues It becomes inflamed, causing warmth, redness, swelling, and pain & unable to move freely As the disease progresses, the inflamed synovium invades and damages the cartilage and bone of the joint. Surrounding muscles, ligaments, and tendons become weakened This process eventually leads to deformity and destruction of the joints RA also can cause more generalized bone loss that may lead to osteoporosis (fragile bones that are prone to fracture)

EPIDEMIOLOGY :

EPIDEMIOLOGY The incidence of RA is in the region of 3 cases per 10,000 population per annum. Onset is uncommon under the age of 15 and from then on the incidence rises with age until the age of 80 Some Native American groups have higher prevalence rates (5–6%) and people from the Carribean region have lower prevalence rates First-degree relatives prevalence rate is 2–3% and disease genetic concordance in monozygotic twins is approximately 15–20%

EPIDEMIOLOGY IN INDIA:

EPIDEMIOLOGY IN INDIA The target population comprised 44,551 adults (over 16 years old). These cases were then further evaluated by the authors using the 1987 revised ARA criteria for the diagnosis of RA A response rate of 89.5% was obtained and 3393 persons listed as possible cases of RA by the health workers Of these, 299 satisfied the revised ARA criteria for the diagnosis of RA, giving a prevalence of 0.75%. The prevalence of RA in India is quite similar to that reported from the developed countries. It is higher than that reported from China, Indonesia, Philippines and rural Africa.

AETIOLOGY :

AETIOLOGY The cause of RA is unknown. It is assumed that a genetically susceptible host is exposed to an unknown antigen & this interaction gives rise to a persistent immunological response The activation of immune response is triggered by the following factors. They are:- GENETIC FACTORS : - RA is documented by presence of immune cell reactivity and production of antibodies to endogenous elements such as immunoglobulins,collagen,andcellular components

CONTD….:

CONTD … . PRESENCE OF HLA (human lymphocyte antigen ):- The most definite genetic association with RA is with HLA alleles.The HLA-DR4 allele is associated with development & severity of RA. Risk of an individual with HLA-DR4 to develop the disease is between 2 & 6. In American Whites,60-70% of RA patients are positive for HLA-DR4. Frequency of this allele among Dutch patients is greater than 90%.

CONTD…:

CONTD … There is a 30% concordance in monozygotic twins compared to 5% in fraternal twins and first degree relatives. First degree relatives of patients develop RA at 4-6 times the rate of standard population rate. INFECTIOUS FACTORS :- Presence of Epstein-Barr virus as antigen. Of patients with RA ,80% have a circulating antibody directed against antigens specific for this virus. Parvovirus particularly B19 & also Mycobacteria(as it expresses HSP,heat sensitive protein)have been linked to RA.

CONTD…:

CONTD… ENDOCRINOLOGIC FACTORS : -. disease may improve during pregnancy and flare after pregnancy. Breastfeeding may also aggravate the disease Contraceptive use reduces the risk of developing RA. This suggests possible deficiencies or changes in certain hormones, may promote the development of RA ENVIRONMENTAL FACTORS :- Changes in barometric pressures are associated with acute worsening of RA. Besides climate,diet,trauma are also known to influence RA.

PATHOGENESIS :

PATHOGENESIS RA is characterised by the infilteration of various inflammatory cells into the joint The synovial membrane becomes highly vascularised & synovial fibroblasts proliferate & inflammatory cells release numerous CYTOKINES & GROWTH FACTORS into the joint These agents cause synovial cells to release proteolytic enzymes &Proliferating inflammatory tissue (PANNUS-tissue serving as origin of joint erosions) subsequently leads to the destruction of intra articular & peri articular structures leading to the joint deformities and dysfunction

FLOW CHART :

FLOW CHART ANTIGEN(??MICROBE) MHC Class II. Gen.susceptibility( CD 4+Tcells) CYTOKINES Macrophage activation FIBROBLASTS,SYNOVIAL CELLS, CHONDROCYTES (proliferation) RELEASE OF COLLAGENASES,PGE2 AND OTHER ENZYMES PANNUS FORMATION,DESTRUCTION OF BONE & CARTILAGE,FIBROSIS,ANKYLOSIS .

FLOW CHART(B CELL ACTIVATN):

FLOW CHART(B CELL ACTIVATN) CYTOKINES B-CELL ACTIVATION FORMATION OF RA FACTOR IMMUNE COMPLEX FORMATION & DEPOSITION JOINT INJURY PANNUS FORMATION, DESTRUCTION OF BONE & CARTILAGE: FIBROSIS, ANKYLOSIS

INFLAMMATORY RESPONSE:

INFLAMMATORY RESPONSE

RISK FACTORS:

RISK FACTORS Gender Age Family history Smoking Overweight HLA gene

DISTINCTIVE CLINICAL FEATURES OF RA:

DISTINCTIVE CLINICAL FEATURES OF RA Tender, warm, swollen joints Symmetrical pattern of affected joints Joint inflammation often affecting the wrist and finger joints closest to the hand Joint inflammation sometimes affecting other joints, including the neck, shoulders, elbows, hips, knees, ankles, and feet Fatigue, occasional fevers, a general sense of not feeling well Pain and stiffness lasting for more than 30 minutes in the morning or after a long rest Variability of symptoms among people with the disease

SYMMETRICAL PATTERN OF AFFECTED JOINTS:

SYMMETRICAL PATTERN OF AFFECTED JOINTS

COMPLICATIONS:

COMPLICATIONS Since RA is a systemic disease, its inflammation can affect organs and areas of the body other than the joints like eyes,skin,lungs,heart & blood vessels Examples of other areas that may be affected include:- SJOGREN’S SYNDROME : -inflammation of the glands of the eyes and mouth and causes dryness of these areas PLEURITIS causes chest pain with deep breathing or coughing Tissue inflammation surrounding the heart, PERICARDITIS

Slide 21:

Rheumatoid disease can reduce the number of red blood cells ANEMIA and white blood cells. Decreased white cells can be associated with an enlarged spleen i.e FELTY'S SYNDROME and can increase the risk of infections. RHEUMATOID NODULES can occur around the elbows and fingers where there is frequent pressure. VASCULITIS rare and serious complication is blood-vessel inflammation which can impair blood supply to tissues and lead to tissue death. This is most often initially visible as tiny black areas around the nail beds or as leg ulcers.

Sjogren’s syndrome, pericarditis,rheumatoid nodules,cutaneous ulcer, Felty’s syndrome :

Sjogren’s syndrome, pericarditis,rheumatoid nodules,cutaneous ulcer, Felty’s syndrome

PLEURITIS,VASCULITIS:

PLEURITIS,VASCULITIS

EROSIVE CHANGES GIVE RISE TO JOINT INSTABILITY &SUBLUXATION.CHARACTERISTIC DEFORMITIES INCLUDE ULNAR DEVIATION,SWAN NECK,BOUTONNIERE SYNDROME.:

EROSIVE CHANGES GIVE RISE TO JOINT INSTABILITY &SUBLUXATION.CHARACTERISTIC DEFORMITIES INCLUDE ULNAR DEVIATION,SWAN NECK,BOUTONNIERE SYNDROME .

INVESTIGATIONS:

INVESTIGATIONS Are made after a full medical and family history and physical and diagnostic testing are evaluated by a qualified health care professional. Medical testing may include a wide variety of tests like:- ESR (Erythrocyte Sedimentation Rate CRP (C – Reactive prot ) INFLAMMATORY RF (Rheumatoid factor)blood tests MARKERS ANA (Anti nuclear antibodies) JOINT X-RAYS MRI (Magnetic resonance imaging) & US (ultra sou nd)

CONTD…:

CONTD … ESR … It is a test that measures how fast red blood cells (erythrocytes) drop to the bottom of a collection tube. CRP … C-reactive protein, another common test for inflammation is useful both in making a diagnosis and monitoring disease activity and response to anti-inflammatory therapy. RA FACTOR … is an autoantibody that is present in the blood of most people with RA & directed against host immunoglobulin & present in 75-80% in patients with RA.

CONTD…:

CONTD … ANA ….These are investigated to rule out possibility of other connective tissue disorders like SLE. ANA’s are raised in 80% of patients with SLE & 20% of patients with RA. X-RAYS ….Erosions can be seen at the joint margins & loss of joint space due to erosion of cartilage & bone may be identified. MRI & US SCAN …used to detect inflammatory activity. so these are increasingly used to detect early changes in RA patients .

CONTD…:

CONTD … Laboratory tests include an elevated alkaline phosphatase, elevated platelet count, decreased serum albumin level Anti-CCP antibodies : This blood test detects antibodies to cyclic citrullinated peptide (anti-CCP). This test is positive in most people with RA and can even be positive years before rheumatoid arthritis symptoms develop.

TREATMENT :

TREATMENT Goals of Treatment Relieve pain Reduce inflammation Slow down or stop joint damage Improve a person's sense of well-being and ability to function. Current Treatment Approaches Lifestyle Medications Surgery Routine monitoring and ongoing care.

NON-PHARMACOLOGICAL TREATMENT:

NON-PHARMACOLOGICAL TREATMENT Physiotherapy is a vital part of treating RA Heat,cold and electrotherapy helps to reduce pain and swelling program of exercise strengthens joints & minimize deformity and increase the range of movement and functions Natural treatments include using massage with herbs,magneto therapy etc Occupational therapy educates patients to protect joints with the use of appliances and splints. Surgical techniques can be effective in relieving pain and restoring function.

PHARMACOLOGICAL TREATMENT:

PHARMACOLOGICAL TREATMENT ANALGESICS –used only for pain relief Eg:-Paracetamol-325 to 650mg every 4-6hrs or 1gm 3-4 times/day Topical Analgesic(Capsaicin)-apply 3-4 times/day NSAID’s -used as an adjunct along with DMARD’s to reduce the inflammation Eg:-Ibuprofen-1.2-3.2 gms/day in 4 divided doses TID Aspirin-325-650mg for every 4hrs for pain 3,600mg for inflammation 4 times daily NSAID’S mainly act by inhibiting COX -1 &2 enzymes blocking COX enzyme site & thus reduces inflamation

CONTD…:

CONTD … CORTICOSTEROIDS - used because of their anti inflammatory & immunosuppressive property Eg:-Prednisone & methyl prednisolone given orally or IV,IM-7.5mg daily as single dose/infusion -Act by suppressing the cytokines DMARD, s (disease modifying anti-rheumatic drugs)-used to slow down the progression of disease These include METHOTREXATE-5 to 25 mg once weekly;Oral or IM SULFASALAZINE-initially 500mg OD,increasing in weekly steps 0f 500mg to 1gm BD

CONTD…….:

CONTD ……. GOLD SODIUM THIOMALATE-10mg test dose,then 50mg weekly & reduce to monthly ;IM HYDROXY CHLOROQUINE--Oral 200-300mgBID,after 1,2 months reduce to 200mg BID AZATHIOPRINE—Oral 50-150 mg daily LEFLUNOMIDE---10-20mg/day as maintenance dose Oral CICLOSPORINE—Oral 2.5mg/kg/day

CURRENT MEDICATIONS:

CURRENT MEDICATIONS BIOLOGICALRESPONSEMODIFIERS — genetically engineered medications that reduce inflammation and structural damage to the joints Eg’s include Etanercept (Enbrel)—50mg SC weekly, Infliximab (Remicade)—3mg/kg IV at 0,2,6 weeks Adalimumab (Humira)—40mg SC for 2 weeks, Reduce inflammation by blocking tumor necrosis factor (TNF), a cytokine or immune system protein that triggers inflammation during normal immune responses

CONTD..:

CONTD.. Anakinra (Kineret), works by blocking a cytokine called interleukin-1 (IL-1) that is seen in excess in patients with RA Rituximab (Rituxan) stops the activation of a type of white blood cell called B cells. Abatacept (Orencia) blocks a particular chemical that triggers the overproduction of white blood cells called T cells that play a role in inflammation Tociluzimab a humanised MAb to IL-6 is a proinflammatory cytokine & prevents erosion & joint space narrowing

CURRENT SURGERY APPROACHES:

CURRENT SURGERY APPROACHES The primary purpose is to reduce pain, improve the affected joint’s function, and improve the patient’s ability to perform daily activities Joint replacement :involves removing all or part of a damaged joint and replacing it with synthetic components. Most commonly replaced joints are the hips and knees.

HIP REPLACEMENT :

HIP REPLACEMENT

KNEE REPLACEMENT :

KNEE REPLACEMENT

CONTD……:

CONTD …… Arthrodesis (fusion): is a surgical procedure that involves removing the joint and fusing the bones into one immobile unit, often using bonegrafts from the person’s own pelvis useful for increasing stability and relieving pain in affected joints Tendon reconstruction : RA can damage and even rupture tendons, the tissues that attach muscle to bone reconstructs the damaged tendon by attaching an intact tendon to it

DIAGRAM SHOWING ARTHODESIS:

DIAGRAM SHOWING ARTHODESIS

DIAGRAM SHOWING TENDON RECONSTRUCTION:

DIAGRAM SHOWING TENDON RECONSTRUCTION

GENERAL APPRAOCHES:

GENERAL APPRAOCHES Routine monitoring and ongoing care: Regular medical care is important to monitor the course of the disease, determine the effectiveness and any negative effects of medications, and change therapies as needed Healthful diet :- overall nutritious diet with enough—but not an excess of—calories, protein, and calcium is important Those taking methotrexate need to avoid alcohol as most serious long-term side effects is liver damage

CONTD….:

CONTD …. Stress reduction :- Stress also may affect the amount of pain a person feels Regular rest periods can help, as can relaxation, distraction, or visualization exercises Joint care :- using a splint for a short time around a painful joint reduces pain and swelling by supporting the joint and letting it rest Rest and exercise :- good balance between rest and exercise is required They reduce active joint inflammation and pain and to fight fatigue,maintaining healthy and strong muscles, preserving joint mobility, and maintaining flexibility

prevention:

prevention There is no known way to prevent RA because the exact cause of the disease is not known Preventive measures can be taken only after diagnosis of the disease. But making some modifications in :- Diet(consume nutritious food ) Relaxed Life style Avoiding smoking & alcohol consumption Maintaining ideal body weight Exercises likeswimming,cycling,yoga can prevent the increased risk of RA .

CONCLUSION:

CONCLUSION RA is the most common inflammatory disease affecting 1% of population & can affect virtually every area of a person’s life from work life to family life One study showed that more than a quarter of women stopped working within 4 years after being diagnosed with rheumatoid arthritis &also interferes with the joys and responsibilities of family life Fortunately, current treatment strategies, including pain-relieving drugs and medications that slow joint damage, a balance between rest and exercise, and patient education and support programs, allow most people with the disease to lead active and productive lives

REFERENCES:

REFERENCES Text Book of Clinical Pharmacy & Therapeutics By Roger Walker,Cate Whittlesea,4 th edition Text Book of Basic Pathology Cotran,Robbins,Vinay kumar 6 th edition Text Book of Pharmacotherapy,7 th edition By Joseph T.Dipiro www.hopkins-arthritis.com www.pubmed.gov www.arthritis.about.com www.niams.nih.gov www.wrongdiagnosis.com www.medicinenet.com www.goldbamboo.com/pictures

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